Summary of Study ST001075

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000720. The data can be accessed directly via it's Project DOI: 10.21228/M8M977 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Show all samples  |  Perform analysis on untargeted data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST001075
Study TitleIntegrated metabolome and transcriptome analyses provide novel insight into colon cancer modulation by the gut microbiota
Study SummaryColon cancer onset and progression is strongly associated with the presence, absence, or relative abundances of certain microbial taxa in the gastrointestinal tract. However, specific mechanisms affecting disease susceptibility related to complex commensal bacterial mixtures are poorly understood. We used a multi-omics approach to determine how differences in the complex gut microbiome (GM) influence the metabolome and host transcriptome and ultimately affect susceptibility to adenoma development. Fecal samples collected from a preclinical rat model of colon cancer harboring distinct complex GMs were analyzed using ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS). We collected samples prior to observable disease onset and identified putative metabolite profiles that predicted future disease severity, independent of GM status. Transcriptome analyses performed after disease onset from normal epithelium and tumor tissues between the high and low tumor GMs suggests that the GM is also correlated with altered host gene expression. Integrated pathway (IP) analyses of the metabolome and transcriptome based on putatively identified metabolic features indicate that bile acid biosynthesis was enriched in rats with high tumors (GM:F344) along with increased fatty acid metabolism and mucin biosynthesis. These data emphasize the utility of using untargeted metabolomics to reveal signatures of susceptibility and resistance and integrated analysis reveals common pathways that are likely to be universal targets for intervention.
Institute
University of Missouri-Columbia
Last NameBusi
First NameSusheel Bhanu
Address4011 Discovery Drive N121
EmailSB6F4@MAIL.MISSOURI.EDU
Phone2404094390
Submit Date2018-10-10
Num Groups3
Total Subjects13
Raw Data AvailableYes
Raw Data File Type(s)cdf
Analysis Type DetailGC-MS
Release Date2019-01-22
Release Version1
Susheel Bhanu Busi Susheel Bhanu Busi
https://dx.doi.org/10.21228/M8M977
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR000720
Project DOI:doi: 10.21228/M8M977
Project Title:Integrated metabolome and transcriptome analyses provide novel insight into colon cancer modulation by the gut microbiota
Project Summary:Colon cancer onset and progression is strongly associated with the presence, absence, or relative abundances of certain microbial taxa in the gastrointestinal tract. However, specific mechanisms affecting disease susceptibility related to complex commensal bacterial mixtures are poorly understood. We used a multi-omics approach to determine how differences in the complex gut microbiome (GM) influence the metabolome and host transcriptome and ultimately affect susceptibility to adenoma development. Fecal samples collected from a preclinical rat model of colon cancer harboring distinct complex GMs were analyzed using ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS). We collected samples prior to observable disease onset and identified putative metabolite profiles that predicted future disease severity, independent of GM status. Transcriptome analyses performed after disease onset from normal epithelium and tumor tissues between the high and low tumor GMs suggests that the GM is also correlated with altered host gene expression. Integrated pathway (IP) analyses of the metabolome and transcriptome based on putatively identified metabolic features indicate that bile acid biosynthesis was enriched in rats with high tumors (GM:F344) along with increased fatty acid metabolism and mucin biosynthesis. These data emphasize the utility of using untargeted metabolomics to reveal signatures of susceptibility and resistance and integrated analysis reveals common pathways that are likely to be universal targets for intervention.
Institute:University of Missouri
Department:Veterinary Pathobiology
Laboratory:Amos-Landgraf
Last Name:Busi
First Name:Susheel Bhanu
Address:4011 Discovery Drive, N121
Email:sb6f4@mail.missouri.edu
Phone:2404094390
Contributors:Zhentian Lei, James Amos-Landgraf, Lloyd W. Sumner,

Subject:

Subject ID:SU001119
Subject Type:Mammal
Subject Species:Rattus norvegicus
Taxonomy ID:10116
Genotype Strain:F344/Ntac-Apc-+/Pirc
Age Or Age Range:30
Animal Animal Supplier:Taconic and Envigo
Animal Housing:Conventional,
Animal Feed:Labdiet 5058
Animal Water:Autoclaved, purified with sulfuric acid

Factors:

Subject type: Mammal; Subject species: Rattus norvegicus (Factor headings shown in green)

mb_sample_id local_sample_id Group
SA072510SB4GM;F344
SA072511SB3GM;F344
SA072512SB1GM;F344
SA072513SB2GM;F344
SA072514SB8GM;LEW
SA072515SB7GM;LEW
SA072516SB6GM;LEW
SA072517SB5GM;LEW
SA072518SB12GM;SD
SA072519SB13GM;SD
SA072520SB11GM;SD
SA072521SB9GM;SD
SA072522SB10GM;SD
Showing results 1 to 13 of 13

Collection:

Collection ID:CO001113
Collection Summary:Fecal samples collected at 1 month of age, prior to any observable disease onset. F344 refers to Fisher (F344) rats, whereas as GM:SD refers to the GM from Sprague-Dawley rats, while GM:LEW refers to the gut microbiota (GM) from Lewis rats
Collection Protocol ID:8732
Sample Type:Feces
Collection Method:Sterile, asceptic method. Animals were placed in clean, sterile cages and feces were speared with sterile, autoclaved toothpicks.
Collection Location:Discovery Ridge, Columbia MO
Storage Conditions:-80℃
Collection Vials:Glass
Storage Vials:Glass

Treatment:

Treatment ID:TR001133
Treatment Summary:Pirc rats were rederived using 3 surrogate dams, each with distinct gut microbiota profiles
Treatment Protocol ID:8732

Sample Preparation:

Sampleprep ID:SP001126
Sampleprep Summary:Fecal samples were lyophilized at -20 ˚C using 0.1 millibar of vacuum pressure, following which dried samples (30 mg) were extracted sequentially for both UHPLC-MS and GC-MS. The dried samples were first treated with 1.0 mL of 80% MeOH containing 18 µg/mL umbelliferone, sonicated for 5 minutes and centrifuged for 40 minutes at 3000 g at 10 ºC. 0.5 mL of supernatant was used for UHPLC-MS analysis after a subsequent spin at 5000 g at 10 ºC for 20 minutes and transferring 250 µL of the sample into glass autosampler vials with inserts. For GC-MS (Gas Chromatography-Mass Spectrometry) analyses of primary polar metabolites, 0.5 mL water was added the remaining extract used above for the UHPLC preparation, sonicated for 5 min, extracted for 30min, and centrifuged at 3000 g. 0.5 mL of the polar extract was subsequently dried under nitrogen and derivatized using previously established protocols (84). Briefly, N-Methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA) with 1 % TMCS (2,2,2-Trifluoro-N-methyl-N-(trimethylsilyl)-acetamide, Chlorotrimethylsilane) was used to derivatize the polar metabolites, after treatment with methoxyamine-HCl-pyridine.

Combined analysis:

Analysis ID AN001757
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 1290
Column Waters Acquity BEH C18 (150 x 2.1mm,1.7um)
MS Type ESI
MS instrument type QTOF
MS instrument name Bruker maXis Impact qTOF
Ion Mode NEGATIVE
Units Peak Area

Chromatography:

Chromatography ID:CH001241
Instrument Name:Agilent 1290
Column Name:Waters Acquity BEH C18 (150 x 2.1mm,1.7um)
Chromatography Type:Reversed phase

MS:

MS ID:MS001625
Analysis ID:AN001757
Instrument Name:Bruker maXis Impact qTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:NEGATIVE
  logo